This project will characterize mechanisms through which glycation of fibronectin impairs the mechanotransduction of adhesion and fluid shear stress by cultured vascular endothelial cells, as a model for events occurring in vivo in the chronic diabetic state. There is a paucity of information regarding the molecular mechanisms of endothelial dysfunction in diabetic blood vessels. Few studies to date have utilized a model of endothelium in the environment of a glycated matrix, and none have explored the regulation of such cells by fluid flow, a major determinant of endothelial function. To acheive these goals, the following Specific Aims are proposed: Aim 1. Grow endothelial cells on glycated recombinant fibronectin and characterize the expression and function of fibronectin and integrins. Aim 2. Determine the effects of fibronectin glycation on endothelial mechanotransduction of shear stress to MAP kinase activation and NO production.